Lecture 3 Dl.ppt

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Lecture 3 Dl.ppt

  1. 1. <ul><li>Lecture 3 </li></ul><ul><li>Voltage-gated channels & the Action Potential </li></ul><ul><li>Channelopathies </li></ul>
  2. 2. Learning Objectives <ul><ul><li>Describe the ion substitution experiments performed by Hodgkin and Huxley in elucidating the ion responsible for the biphasic currents obtained in their voltage clamp experiments with the squid giant axon. What pharmacological agents can also distinguish between these currents? </li></ul></ul><ul><ul><li>Know how to plot and explain the current-voltage relationship of voltage-gated K + and Na + currents. </li></ul></ul><ul><ul><li>Contrast the topology of various voltage-gated channels and discuss their distinguishing structural feature involved in voltage sensitivity. </li></ul></ul><ul><ul><li>Know how is voltage dependence recognized in single-channel records obtained from voltage steps to different potentials. </li></ul></ul><ul><ul><li>Predict the result of an ensemble average of many single-channel current records in response to steps to a particular voltage. </li></ul></ul><ul><ul><li>Plot the probability of Na + channel opening and the Na + current obtained as a function of voltage. </li></ul></ul><ul><ul><li>Describe an action potential in terms of its dependence on the time course of g Na and g K . </li></ul></ul><ul><ul><li>Discuss the mechanism of Na + channel inactivation and its control of the refractory period for generation of multiple action potentials. </li></ul></ul><ul><ul><li>Describe the events taking place in the neuromuscular junction leading to an action potential. </li></ul></ul><ul><ul><li>Physiologic Principles Underlying Ion Channelopathies </li></ul></ul><ul><ul><li>Examples of ion channel dysfunction leading to disease (The TRP channel family and CFTR) </li></ul></ul>
  3. 5. The depolarization-induced biphasic current of squid giant axons
  4. 6. Inward sodium and outward currents
  5. 7. Sodium and Potassium whole-cell currents
  6. 8. Topology of a voltage-gated K + channel
  7. 9. Ion channel topologies
  8. 10. Voltage-gated channels show an increased P o at more depolarized potentials
  9. 11. Non-inactivating K + channel currents
  10. 12. Inactivating Na + channel currents
  11. 13. P o of voltage-gated Na + channels and the resting K + conductance
  12. 14. Effect of K + or Na + channel activation on membrane potential
  13. 15. Mechanism of fast inactivation of voltage-gated channels
  14. 16. The Action Potential (AP) of a Squid Giant Axon
  15. 17. The neuromuscular junction
  16. 18. Signaling in the neuromuscular junction
  17. 19. Atomic Resolution Structures Voltage-dependent gating
  18. 20. Long SB, Campbell EB, Mackinnon R. Crystal structure of a mammalian voltage-dependent Shaker family K + channel. Science. 2005;309:897-903
  19. 25. Channelopathies

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